Gonadotropin
Encyclopedia
Gonadotropins are protein
hormone
s secreted by gonadotrope cells of the pituitary gland
of vertebrate
s. This is a family of proteins, which include the mammalian hormones follitropin (FSH), lutropin (LH), placental chorionic gonadotropins hCG and eCG and chorionic gonadotropin (CG), as well as at least two forms of fish gonadotropins. These hormones are central to the complex endocrine system
that regulates normal growth, sexual development, and reproductive function. The hormones LH and FSH are secreted by the anterior pituitary gland
, while hCG and eCG are secreted by the placenta
.
Gonadotropin is sometimes abbreviated Gn. The British spelling is gonadotrophin.
(LH) and follicle-stimulating hormone
(FSH), although primates produce a third gonadotropin called chorionic gonadotropin (CG). LH and FSH are heterodimers consisting of two peptide
chains, an alpha chain
and a beta chain. LH and FSH share nearly identical alpha chains (about 100 amino acids long), whereas the beta chain provides specificity for receptor
interactions. These subunits are heavily modified by glycosylation
.
The alpha subunit is common to each protein dimer (well conserved within species, but differing between them), and a unique beta subunit, which confers biological specificity. The alpha chains are highly conserved proteins of about 100 amino acid residues which contain ten conserved cysteines all involved in disulfide bonds, as shown in the following schematic representation.
+---------------------------+
+----------+| +-------------|--+
| || | | |
xxxxCxCxxxxxxCxCCxxxxxxxxxxxxxCCxxxxxxxxxxCxCxxCx
| | | |
+------|-----------------+ |
| |
+----------------------------+
'C': conserved cysteine involved in a disulphide bond.
Intracellular levels of free alpha subunits are greater than those of the mature glycoprotein, implying that hormone assembly is limited by the appearance of the specific beta subunits, and hence that synthesis of alpha and beta is independently regulated.
Another human gonadotropin is human chorionic gonadotropin
(hCG), produced by the placenta
during pregnancy
.
s and coupled to the G-protein system. Signals triggered by binding to the receptor are relayed within the cells by the cyclic AMP second messenger system.
Gonadotropins are released under the control of gonadotropin-releasing hormone
(GnRH) from the arcuate nucleus and preoptic area of the hypothalamus
. The gonad
s — testes and ovaries
— are the primary target organs for LH
and FSH
. The gonadotropins affect multiple cell types and elicit multiple responses from the target organs. As a simplified generalization, LH
stimulates the Leydig cells of the testes and the theca cells of the ovaries to produce testosterone
(and indirectly estradiol
), whereas FSH
stimulates the spermatogenic tissue of the testes and the granulosa cell
s of ovarian follicle
s.
, which can lead to infertility
. Treatment includes administered gonadotropins, which, therefore, work as fertility medication
. Such can either be produced by extraction and purification from urine or be produced by recombinant DNA
.
Failure or loss of the gonads usually results in elevated levels of LH and FSH in the blood.
. For example, the so called menotropin
s (also called human menopausal gonadotropins) consist of LH
and FSH
extracted from human urine
from menopausal women. There are also recombinant variants.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
s secreted by gonadotrope cells of the pituitary gland
Pituitary gland
In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...
of vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...
s. This is a family of proteins, which include the mammalian hormones follitropin (FSH), lutropin (LH), placental chorionic gonadotropins hCG and eCG and chorionic gonadotropin (CG), as well as at least two forms of fish gonadotropins. These hormones are central to the complex endocrine system
Endocrine system
In physiology, the endocrine system is a system of glands, each of which secretes a type of hormone directly into the bloodstream to regulate the body. The endocrine system is in contrast to the exocrine system, which secretes its chemicals using ducts. It derives from the Greek words "endo"...
that regulates normal growth, sexual development, and reproductive function. The hormones LH and FSH are secreted by the anterior pituitary gland
Pituitary gland
In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...
, while hCG and eCG are secreted by the placenta
Placenta
The placenta is an organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. "True" placentas are a defining characteristic of eutherian or "placental" mammals, but are also found in some snakes and...
.
Gonadotropin is sometimes abbreviated Gn. The British spelling is gonadotrophin.
Natural types and subunit structure
The two principal gonadotropins in vertebrates are luteinizing hormoneLuteinizing hormone
Luteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...
(LH) and follicle-stimulating hormone
Follicle-stimulating hormone
Follicle-stimulating hormone is a hormone found in humans and other animals. It is synthesized and secreted by gonadotrophs of the anterior pituitary gland. FSH regulates the development, growth, pubertal maturation, and reproductive processes of the body. FSH and Luteinizing hormone act...
(FSH), although primates produce a third gonadotropin called chorionic gonadotropin (CG). LH and FSH are heterodimers consisting of two peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
chains, an alpha chain
Chorionic gonadotropin alpha
Glycoprotein hormones alpha chain is a protein that in humans is encoded by the CGA gene.-Further reading:...
and a beta chain. LH and FSH share nearly identical alpha chains (about 100 amino acids long), whereas the beta chain provides specificity for receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
interactions. These subunits are heavily modified by glycosylation
Glycosylation
Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules...
.
The alpha subunit is common to each protein dimer (well conserved within species, but differing between them), and a unique beta subunit, which confers biological specificity. The alpha chains are highly conserved proteins of about 100 amino acid residues which contain ten conserved cysteines all involved in disulfide bonds, as shown in the following schematic representation.
+---------------------------+
+----------+| +-------------|--+
| || | | |
xxxxCxCxxxxxxCxCCxxxxxxxxxxxxxCCxxxxxxxxxxCxCxxCx
| | | |
+------|-----------------+ |
| |
+----------------------------+
'C': conserved cysteine involved in a disulphide bond.
Intracellular levels of free alpha subunits are greater than those of the mature glycoprotein, implying that hormone assembly is limited by the appearance of the specific beta subunits, and hence that synthesis of alpha and beta is independently regulated.
Another human gonadotropin is human chorionic gonadotropin
Human chorionic gonadotropin
Human chorionic gonadotropin or human chorionic gonadotrophin is a glycoprotein hormone produced during pregnancy that is made by the developing embryo after conception and later by the syncytiotrophoblast .. Some tumors make this hormone; measured elevated levels when the patient is not...
(hCG), produced by the placenta
Placenta
The placenta is an organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. "True" placentas are a defining characteristic of eutherian or "placental" mammals, but are also found in some snakes and...
during pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
.
Mechanism
Gonadotropin receptors are embedded in the surface of the target cell membraneCell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
s and coupled to the G-protein system. Signals triggered by binding to the receptor are relayed within the cells by the cyclic AMP second messenger system.
Gonadotropins are released under the control of gonadotropin-releasing hormone
Gonadotropin-releasing hormone
Gonadotropin-releasing hormone , also known as Luteinizing-hormone-releasing hormone and luliberin, is a tropic peptide hormone responsible for the release of follicle-stimulating hormone and luteinizing hormone from the anterior pituitary. GnRH is synthesized and released from neurons within...
(GnRH) from the arcuate nucleus and preoptic area of the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
. The gonad
Gonad
The gonad is the organ that makes gametes. The gonads in males are the testes and the gonads in females are the ovaries. The product, gametes, are haploid germ cells. For example, spermatozoon and egg cells are gametes...
s — testes and ovaries
Ovary
The ovary is an ovum-producing reproductive organ, often found in pairs as part of the vertebrate female reproductive system. Ovaries in anatomically female individuals are analogous to testes in anatomically male individuals, in that they are both gonads and endocrine glands.-Human anatomy:Ovaries...
— are the primary target organs for LH
Luteinizing hormone
Luteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...
and FSH
Follicle-stimulating hormone
Follicle-stimulating hormone is a hormone found in humans and other animals. It is synthesized and secreted by gonadotrophs of the anterior pituitary gland. FSH regulates the development, growth, pubertal maturation, and reproductive processes of the body. FSH and Luteinizing hormone act...
. The gonadotropins affect multiple cell types and elicit multiple responses from the target organs. As a simplified generalization, LH
Luteinizing hormone
Luteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...
stimulates the Leydig cells of the testes and the theca cells of the ovaries to produce testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
(and indirectly estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
), whereas FSH
Follicle-stimulating hormone
Follicle-stimulating hormone is a hormone found in humans and other animals. It is synthesized and secreted by gonadotrophs of the anterior pituitary gland. FSH regulates the development, growth, pubertal maturation, and reproductive processes of the body. FSH and Luteinizing hormone act...
stimulates the spermatogenic tissue of the testes and the granulosa cell
Granulosa cell
A granulosa cell or follicular cell is a somatic cell of the sex cord that is closely associated with the developing female gamete in the ovary of mammals.-Anatomy and function:...
s of ovarian follicle
Ovarian follicle
Ovarian follicles are the basic units of female reproductive biology, each of which is composed of roughly spherical aggregations of cells found in the ovary. They contain a single oocyte . These structures are periodically initiated to grow and develop, culminating in ovulation of usually a single...
s.
Diseases
Gonadotropin deficiency due to pituitary disease results in hypogonadismHypogonadism
Hypogonadism is a medical term for decreased functional activity of the gonads. Low testosterone is caused by a decline or deficiency in gonadal production of testosterone in males...
, which can lead to infertility
Infertility
Infertility primarily refers to the biological inability of a person to contribute to conception. Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term...
. Treatment includes administered gonadotropins, which, therefore, work as fertility medication
Fertility medication
Fertility medication are drugs which enhance reproductive fertility. For women, fertility medication is used to stimulate follicle development of the ovary...
. Such can either be produced by extraction and purification from urine or be produced by recombinant DNA
Recombinant DNA
Recombinant DNA molecules are DNA sequences that result from the use of laboratory methods to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in biological organisms...
.
Failure or loss of the gonads usually results in elevated levels of LH and FSH in the blood.
Pharmacologic preparations
There are various preparations of gonadotropins for therapeutic use, mainly as fertility medicationFertility medication
Fertility medication are drugs which enhance reproductive fertility. For women, fertility medication is used to stimulate follicle development of the ovary...
. For example, the so called menotropin
Menotropin
Menotropin is an active substance for the treatment of fertility disturbances. It consists of gonadotropins that are extracted from the urine of postmenopausal women, usually luteinizing hormone and follicle-stimulating hormone...
s (also called human menopausal gonadotropins) consist of LH
Luteinizing hormone
Luteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...
and FSH
Follicle-stimulating hormone
Follicle-stimulating hormone is a hormone found in humans and other animals. It is synthesized and secreted by gonadotrophs of the anterior pituitary gland. FSH regulates the development, growth, pubertal maturation, and reproductive processes of the body. FSH and Luteinizing hormone act...
extracted from human urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
from menopausal women. There are also recombinant variants.